Ex Parte Finegold

Patent Trial and Appeal Board

Sep 29, 2014

11979007 (P.T.A.B. Sep. 29, 2014)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/979,007 10/30/2007 Sydney M. Finegold 30452.14USC1 5473
7590 09/30/2014
Adriano & Associates
Suite 203
572 East Green Street
Pasadena, CA 91101
EXAMINER
TONGUE, LAKIA J
ART UNIT PAPER NUMBER
1645
MAIL DATE DELIVERY MODE
09/30/2014 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte SYDNEY M. FINEGOLD1
__________

Appeal 2012-005983
Application 11/979,007
Technology Center 1600
__________

Before ULRIKE W. JENKS, CHRISTOPHER G. PAULRAJ, and
ROBERT A. POLLOCK, Administrative Patent Judges.

Opinion for the Board filed by Administrative Patent Judge POLLOCK.

Dissenting Opinion filed by Administrative Patent Judge PAULRAJ.

POLLOCK, Administrative Patent Judge.

DECISION ON APPEAL
Appellant appeals under 35 U.S.C. § 134(a) from the Examiner’s
Final Rejection of claims 15 and 21–26 as unpatentable under 35 U.S.C. §
112, first paragraph. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.

1 According to Appellant, the Real Party in Interest is The United States
Department of Veterans Affairs. (App. Br. 2).
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STATEMENT OF THE CASE
Appellant’s invention relates to the treatment of autism in a subset of
affected children having pathogenic, neurotoxic bacteria colonizing the
gastrointestinal tract. (See e.g., Spec. 2:22–30; 4:9–23; 20:11–20.)
Representative independent claim 15 (formatted) reads as follows:
15. A method of treating autism associated with colonization of
pathogenic bacteria in the gastrointestinal tract of a patient, said
method comprising
administering to the patient suffering from autism a treatment
course of an effective amount of metronidazole, bacitracin, or
vancomycin
thereby treating autism associated with colonization of
pathogenic bacteria in the gastrointestinal tract of a patient.
The following grounds of rejection are before us for review:
Claims 15 and 21–26 are rejected under 35 U.S.C. § 112, first
paragraph as lacking enablement.
FINDINGS OF FACT
Bacterial infection has been linked to a number of conditions affecting
the nervous system. Clostridium tetani bacteria, the causative agent of
tetanus (lockjaw) in humans, release an exotoxin called tetanospasmin,
which travels through neurons resulting in nervous system irregularities
including constant skeletal muscle contraction. (Spec. 5:6–19.) Another
condition caused by bacterial infection, D-lactic acidosis, results from
changes in intestinal bacteria to acid-tolerant, aciduric flora. (Id. 21:4–8.)
D-lactic acidosis presents as “a range of behavioral changes such as
hostility, slurred speech, stupor, altered mental status, dizziness, asterixis,
and ataxia” wherein, treatment with oral antimicrobials “result[s] in rapid
cessation of neurological signs.” (Id. 21:8–11.)
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The Specification posits a “‘gut-brain’ etiologic connection” (id.
20:11–16) wherein “pathogenic proliferation of microbes in the gut can at
least partially cause deleterious neurological symptoms and syndromes of
many disorders, including at least some forms of Pervasive Development
Disorder including both Early-Onset and Late-Onset Autism . . . .” (Id.
4:21–23). Consistent with this hypothesis, the Specification points to
observational reports of children with “repeated broad-spectrum
antimicrobial use (usually for chronic otitis media), followed by chronic
diarrhea, then loss of language, play, and social skills, and subsequent onset
of autistic symptoms.” (Id. 15:4–6.)
Applicant reasons that “repeated antimicrobial use may have disrupted
a protective effect of indigenous intestinal organisms and allowed
colonization by one or more neurotoxin-producing species.” (Id. 15:6–8.)
The Specification identifies members of the genus Clostridium, including C.
tetani, C. botulinum, C. perfringens, and C. difficile, as “plausible agents of
these neurological disorders, because several members of this genus are
known to produce neurotoxins, they proliferate enterically during
antimicrobial therapy (e.g., C. difficile), and they have been implicated in
diarrheal diseases of humans and animals.” (Id. 5:7–6:7.)
The Specification notes that intestinal colonization by opportunistic
pathogens such as Clostridium difficile (the causative agent of
pseudomembranous colitis) is greatly enhanced when the protective
intestinal microbiota is disrupted by broad-spectrum antimicrobials. (20:30–
21:2.) The Specification reports that fecal flora samples from four autistic
children previously treated with broad-spectrum antimicrobials, lack
anereobic cocci, chiefly peptostreptococcal species, commonly found in
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adult controls. (Id. 19:1–20:9; 22:4–12.) The Specification states that “[u]se
of normal adult control fecal specimens in the present study, though not
ideal, is justifiable given documented similarity to pediatric stool flora.” (Id.
22:17–19.) Noting that that an uncharacterized Peptostreptococcus species
inhibits clostridia in vitro and in animals, the Specification suggests that “the
absence of such organisms in certain autistic children may permit growth of
clostridial or other toxin-producing bacteria through loss of competitive
inhibition.” (Id. 22:14–16). Thus, “appropriately targeted antimicrobial
therapy might reduce autistic symptoms in these individuals.” (Id. 15:8–9.)
The Specification also discloses evidence that “antibiotic therapy
directed to the proliferating microbial species, results in improved
neurological function through inhibition or elimination of the proliferating
species.” (Id. 4: 9–11.) The Specification discloses an index case involving
a 4.5 year old Caucasian male with chronic diarrhea and autism. (Id. 22:29.)
The subject’s diarrhea began at approximately 17 months of age following a
course of broad spectrum antimicrobials. Social development was normal
until 19 months, “when there was profound behavioral and developmental
deterioration, along with emergence of severe autistic features.” (Id.) The
patient achieved “rapid and dramatic clinical improvement” shortly after the
initiation of a 12-week therapeutic trial of oral vancomycin. (Id.) Shortly
after vancomycin discontinuation, behavioral deterioration was observed and
he eventually lost most of the initial gains. (Id.)
The Specification further discloses the results of an open-label trial
involving eleven autistic children meeting inclusion criteria including a
history of antibiotic use within two months of onset of autism symptoms,
and a history of persistent loose stool, with diarrhea onset before autism
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symptoms. (Id. 16:18–17:12; 14:17–21.) Patients were provided a six-week
treatment with oral vancomycin, followed by four weeks of oral probiotics.
(Id. 17:9–12.) The Specification reports improvements using an analog
rating scale “for the group as a whole in communication (Wilcoxon Signed
Ranks Z = -2.9 p = .003) and behavior (Wilcoxon Signed Ranks Z = -2.9 p =
.003),” as well as additional evidence of improvement for eight of the ten
children independently evaluated by a clinical psychologist. (Id. 17:16–27;
18:6–16; 14:17–26.) The results of this study were published in the peer-
reviewed Journal of Child Neurology.2
The Specification notes that “[a]lthough apparent improvement was
clear by several measures, unfortunately these gains did not endure.” (Id.
18:24–25.) “During telephone follow-up (conducted weekly during the
probiotic therapy), most parents reported substantial behavioral deterioration
within two weeks of discontinuance of vancomycin treatment,” indicating
that “the probiotic therapy used as an adjunct after vancomycin treatment
had no discernible beneficial or adverse effect.” (Id. 18:26–32.) In
discussing the deterioration of behavioral improvements made while on
therapy, the Specification suggests that the decline “is due to the offending
organism being spore-forming, and hence surviving therapy to germinate
after vancomycin discontinuation, as has been documented with Clostridium
difficile infection.” (Id. 21:22–23.) In light of the clinical trial results, the
Specification states that, “[a]lthough the protocol utilized is not suggested as
useful therapy, these results indicate that study of a possible ‘gut-flora’

2 Sandler et al., Short-Term Benefit From Oral Vancomycin Treatment of
Regressive-Onset Autism, 15 J. Child Neurology, 429–434 (2000)
(submitted with Appellant’s brief).
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connection warrants further investigation as it might lead to greater
pathophysiologic insight and meaningful prevention and/or treatment in a
subset of children with autism.” (Id. 14:23–26.)
The Specification states that the use of antibiotics among children and
adults for bacterial infections is “ubiquitous,” (id. 1:19) and makes clear that
treating bacterial infections of the gut with antibiotics is well known. In
addition to the use of oral antibiotics in the treatment of D-lactic acidosis,
discussed above, the specification further teaches that for treating
Clostridium overgrowth in the gut, ramoplanin is preferable to drugs such as
vancomycin and metronidazole, “which have previously been used.” (Spec.
9:7–24).
ANALYSIS
The claims on appeal apply a known treatment against pathogenic
bacteria to a sub-population of patients suffering from the colonization of
pathogenic bacteria in the gastrointestinal tract. In particular, Appellant’s
claims are directed to treating those patients suffering the colonization of
pathogenic bacteria in the gastrointestinal tract who also suffer from autism,
with known antibiotics. The Specification provides sufficient criteria to
identify these patients in the general population (e.g., Spec. 16:18–34;
14:17–21 (study inclusion criteria)) and makes clear that “[t]he treatment to
reduce or eliminate such pathogenic bacteria load is well known in the art.”
(App. Br. 26; see also, e.g., Spec. 9:7–24 (“Ramoplanin is preferable to
drugs such as vancomycin and metronidazole, which have previously been
used.”).) Moreover, the Specification provides both a scientific rationale
that the treatment of certain patients with metronidazole, bacitracin or
vancomycin, could ameliorate autistic symptoms, as well as evidence that
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this treatment does have beneficial (albeit temporary) effects on those
symptoms.

The Examiner finds the Specification not enabling “for a method of
treating autism associated with colonization of pathogenic bacteria in the
gastrointestinal tract of a patient comprising administering to the patient
suffering from autism a treatment course of an effective amount of
metronidazole, bacitracin, vancomycin.” (Ans. 4-5, 9.) At the same time,
the Examiner accepts that:
(1) the Specification is “enabling for a method for suppressing
Clostridium infection in the gastrointestinal tract of an autistic patient
comprising administering to said patient an antimicrobial agent from
the group consisting of metronidazole, bacitracin, or vancomycin”
(Ans. 4);
(2) “there was significant improvement in the symptoms of children with
delayed onset autism by providing them with antibiotics directed
toward common anaerobic intestinal bacteria . . . ” (Ans. 10); and
(3) the “behavior improvement was related to the drugs effect on the
intestinal tract flora . . . ” (id.)
In light of the above, we agree with Appellant that the Examiner has
not set forth a reasonable basis to question the enablement of the claimed
invention. See In re Wright, 999 F.2d 1557, 1562 (Fed. Cir. 1993). In
particular, the Examiner has not established that the Specification did not
teach those skilled in the art how to make and use the full scope of the
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claimed invention without undue experimentation. Genentech, Inc. v. Novo
Nordisk, A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997).3
We find that the Specification provides sufficient evidence of
enablement with respect to treating a subpopulation of patients, those with
autism and suffering from the colonization of pathogenic bacteria in the
gastrointestinal tract. As this is the only question before us on appeal, we
reverse.

SUMMARY
We reverse the rejection of claims 15 and 21–26 under 35 U.S.C.
§112, first paragraph as lacking enablement.

REVERSED

kme

3 While cognizant of the Examiner’s finding that autism is a “complex
severe mental disorder of brain function marked by problems with social
contact, intelligence and language, together with ritualistic or compulsive
behavior and bizarre responses to the environment,” (e.g., Ans. 7) the
Examiner’s statement that autism is not “caused” by bacteria (id.) raises an
issue we need not address here as the instant claims are directed to autism
“associated” with the colonization of pathogenic bacteria in the patient’s
gastrointestinal tract.

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte SYDNEY M. FINEGOLD
__________

Appeal 2012-005983
Application 11/979,007
Technology Center 1600
__________

Before ULRIKE W. JENKS, CHRISTOPHER G. PAULRAJ, and
ROBERT A. POLLOCK, Administrative Patent Judges.

PAULRAJ, Administrative Patent Judge, dissenting.

I respectfully dissent from the Majority’s decision to reverse the lack
of enablement rejection because the Specification does not provide sufficient
guidance for a skilled artisan to practice the full scope of the claimed
treatment method without undue experimentation.
The Majority’s analysis begins with the premise that “Appellant’s
claims are directed to treating those patients suffering the colonization of
pathogenic bacteria in the gastrointestinal tract who also suffer from autism,
with known antibiotics.” (Ante at 6) The plain language of Appellant’s
claims, however, requires “treating autism associated with colonization of
pathogenic bacteria in the gastrointestinal tract of a patient” (Cl. 15
(emphasis added)), and not merely treating bacterial infection in a subset of
autistic patients, by administering an effective amount of metronidazole,
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bacitracin, or vancomycin. Consistent with the Specification (see Findings
of Fact, ante at 2–6), I would interpret the claims to require the actual
treatment of autistic behavior using any of those three antibiotics.
In order for a medical treatment claim to satisfy the enablement
requirement of Section 112, one of ordinary skill in the art must be able to
effectively use the claimed treatment method in order to achieve the desired
therapeutic result. See, e.g., In re ’318 Patent Infringement Litig., 583 F.3d
1317, 1325-27 (Fed. Cir. 2009); Rasmusson v. SmithKline Beecham Corp.,
413 F.3d 1318, 1322-25 (Fed. Cir. 2005). When the claims are directed to a
treatment using a particular drug, “[w]hat is necessary to satisfy the how-to-
use requirement of § 112 is the disclosure of some activity coupled with
knowledge as to the use of this activity.” In re Cortright, 165 F.3d 1353,
1360 (Fed. Cir. 1999) (citation omitted). Appellant’s claims do not satisfy
that standard because the Specification does not establish that all three
recited antibiotics can be used to effectively treat autism. It is insufficient,
in my view, to simply identify patients who happen to suffer from both
autism and pathogenic bacterial infection and reasonably expect to be able to
treat autism by administering those known antibiotics.
At the outset, it is important to recognize both the level of
predictability and the state of the art concerning the treatment of autism as of
the effective filing date. Appellant’s Specification acknowledges that autism
is a “largely untreatable disorder” and that “no underlying etiology can be
identified in the vast number of cases” (Spec. 14 l. 27–32). As found by the
Examiner, “[t]he use of antibiotics for the treatment of autism is not well
known nor is it an art recognized and accepted function of said antibiotics”
(Ans. 6). This is undisputed by Appellant and consistent with the
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Specification’s indication that “the hypothesis that autism (in a defined
subset of children) may be a sequela to the colonization of the intestinal tract
by one or more neurotoxin-producing bacteria is novel . . . . ” (Spec. 20 ll.
17–20 (emphasis added)).
Thus, although Appellant proposed a theory that “an alteration in
colonic flora contributes to autism” based on “a possible ‘gut-brain
etiological connection” (id. at 20 ll. 15–16 (emphasis added)), it was
nonetheless still an unproven theory by the time the priority applications
were filed in 2000 and 2001. A specification that “does no more than state a
hypothesis and propose testing to determine the accuracy of that hypothesis .
. . is not sufficient.” ’318 Patent Infringement Litig., 583 F.3d at 1327; see
also Rasmusson, 413 F.3d at 1325 (“If mere plausibility were the test for
enablement under section 112, applicants could obtain patent rights to
‘inventions’ consisting of little more than respectable guesses as to the
likelihood of their success. . . . That scenario is not consistent with the
statutory requirement that the inventor enable an invention rather than
merely proposing an unproved hypothesis.”); Cortright, 165 F.3d at 1360
(affirming lack of enablement rejection where statements in specification
that applicant “believed” or “surmise[d]” that claimed activity would restore
hair growth “reflect no actual observations”).
To support the enablement of the claims, Appellant relies upon
Example 1 in the Specification, which describes a study in which eleven
autistic children with a history of antimicrobial use and persistent loose
stool/chronic diarrhea were administered a regimen of vancomycin for
several weeks, and videotaped for 30 minutes at baseline and once during
therapy for observation by a clinical child psychologist (Spec. 14–22).
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However, as noted by the Examiner, the study does not identify any control
group to which the observational results were compared (Ans. 16). For
example, the study does not make any comparison to a second group of
similarly situated autistic children that were administered a placebo for the
same period; nor does the study make a comparison to children without
autism that were administered vancomycin for the same period. Appellant
responds that “the children themselves served as their own control on the
effect of oral vancomycin on their autistic condition” (App. Br. 30). But a
comparison to the same children’s own behavior prior to the treatment does
not necessarily indicate that the observed results reflect the treatment of
autism by the administered antibiotic rather than some other cause and/or
effect. The Examiner therefore had good reason to question the results
presented. In re Jolles, 628 F.2d 1322, 1327 (CCPA 1980) (“When utility as
a drug, medicant, and the like in human therapy is alleged, it is proper for
the examiner to ask for substantiating evidence unless one with ordinary
skill in the art would accept the allegations as obviously correct.”).
Moreover, even if the results described in the study were reliable, they only
showed a temporary (short-term) improvement in autistic behavior (Spec. 18
ll. 25–28). Appellant admits based on the subsequent deterioration in
behavior that “[t]he protocol utilized is not suggested as useful therapy”
(Spec. 14 ll. 23–24 (emphasis added)).
Furthermore, even assuming that Example 1 provides an enabling
disclosure for treating autism using the particular protocol disclosed, I do not
believe the full scope of the claimed invention is enabled by that single
example. In re Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991) (“the first
paragraph of § 112 requires that the scope of the claims must bear a
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reasonable correlation to the scope of enablement provided by the
specification”). Example 1 only describes the effect of administering a
single antibiotic, vancomycin, on children with “delayed-onset”
(“regressive” or “late onset”) autism, whereas the claims more broadly
encompass administering any one of three antibiotics—metronidazole,
bacitracin, or vancomycin—to treat either early-onset or delayed-onset
autism (see Cls. 22, 23). The Specification notes that early-onset autism is
“clinically distinct” from delayed-onset autism, and further surmises that
“[c]onventional theories are that there are genetic underpinnings to early
onset autism, but it is more likely in at least some cases there is a
gastrointestinal component” (Spec. 14 ll. 11–14). The Specification,
however, does not provide any evidence that early-onset autism can be
treated in the same manner as delayed-onset autism using antibiotics.1 There
is also no evidence of record that metronidazole and bacitracin have a
sufficient structural similarity with vancomycin, or otherwise would be
expected to work in the same manner as vancomycin to treat either form of
autism. See In re Buting, 418 F.2d 540, 544 (CCPA 1969) (finding evidence
limited to one compound and two types of cancer was not “commensurate
with the broad scope of utility asserted and claimed, viz. that of treating
seven types of cancer with several compounds”); cf. Jolles, 628 F.2d at
1327–28 (structural relationship to known chemotherapy drugs was
sufficient to establish utility for claimed composition and method for
treatment of acute myeloblastic leukemia).

1 Indeed, the Specification does not even present a coherent theory in this
regard as it also indicates that “[t]he invention includes a method of
preventing or treating a gastrointestinal or neurological disorder other than
delayed-onset autism in a patient . . . .” (Spec. 2 ll. 3–5 (emphasis added)).
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For the foregoing reasons, I would affirm the lack of enablement
rejection under 35 U.S.C. 112, ¶ 1.